The role of components of hepatitis B virus (HBV) in the outcome of infection and in the pathogenesis of the resulting disease is unclear. Infected individuals lack circulating interferon and their peripheral blood leukocytes synthesize greatly reduced amounts of interferon. We have obtained data indicating that HBV suppresses the production of biologically active human beta-interferon. Specifically, a 1828 base pair fragment of HBV DNA that contains the genes for the core antigen and for the e antigen acts in a trans-acting manner to cause this suppression. We plan to determine the nature of this HBV trans-acting factor and to ascertain the manner by which it inhibits the transcription of the interferon gene. The minimal HBV DNA sequence necessary to suppress the production of beta-interferon will be determined by subcloning procedures and by BA1 31 exonuclease digestion. Site-directed deletion and point mutations will be generated and used to determine the identity of the HBV trans-acting factor and to elucidate the functional domains within the HBV DNA sequence that are necessary for the suppression of interferon production. Analyses of HBV proteins and RNA present in cells transfected with the mutated HBV DNA should also allow for the identification of the HBV trans-acting factor. Data suggest that the trans-acting factor interacts with the DNA region that regulates the expression of the interferon gene. Thus, the effect of the HBV moiety on various parts of the interferon regulatory DNA region will be examined by the use of deletion mutants of this interferon DNA region. The ability of the HBV trans-acting factor to bind to the regulatory region of the interferon DNA will be investigated by DNA retardation gels and DNase footprinting. Once the HBV trans-acting factor has been identified and its mode of action elucidated, the cellular location of the factor will be determined. The ability of cells to secrete the HBV factor will also be ascertained. The ability of HBV to suppress the synthesis of human alpha interferon will also be examined. It would be of interest to ascertain whether the same segment of HBV DNA would be responsible for the suppression of both alpha and beta- interferons and does so by similar mechanisms. In this manner, information concerning the interaction between hepatitis B virus and interferon can be obtained and may shed some light on the fact that the effectiveness of treatment of chronic hepatitis with interferon is so variable.